This study proposes to characterize in the primate the relationship between pain and temperature primary afferents and spinothalamic neurons, and to study the roles which intraspinal and supraspinal neurons may play as modulators of these connections. Our objective is to provide a structural description of pain relay mechanisms which can be correlated with physiological and pharmacological events in pain sensation. Recently, the neuropeptides substance P and enkephalin, and an indoleamine, serotonin, have been shown to be important agents in the function of spinal cord circuits mediating pain. Substance P may be a transmitter of some nociceptive primary afferents, and enkephalin and serotonin appear to be associated with systems which may reduce pain sensation. The anatomical basis of the function of these substances is little known, particularly in primates and man. By applying immunohistochemical methods, alone and in combination with other anatomical and physiological techniques, precise identification of the elements of the spinal circuits involved in pain may be possible. Previous studies in this laboratory have described the distribution of primary afferents in the primate spinal cord with light microscopy, and the distribution of opiate receptors and their relationships to primary afferents. Current studies are focused on the distribution of substance P, enkephalin, and serotonin in the primate spinal cord and brain stem using light and electron microscopy. Some of our recent findings include - 1) The dual innervation of several classes of human spinal neurons by both substance P and met-enkephalin 2) Localization of substance P in some monkey dorsal horn terminals which are characteristic of primary afferents 3) Localization of enkephalin in mostly axodendritic rather than axoaxonic synaptic contacts in the dorsal horn. 4) Localization of serotonin in the dorsal horn in both axodendritic and axoaxonic contacts 5) The possible identification of serotonin-containing neurons in the monkey spinal cord.